1. Field of the Invention
The present invention relates to a process for the preparation of cyclopropane-1,1-dicarboxylic acid derivatives from malonic acid derivatives and 1,2-dichloro compounds.
2. Description of the Background
Cyclopropane-1,1-dicarboxylic acid derivatives are valuable starting materials for the manufacture of drugs and plant protection agents (see e.g. EP 0 512 211, DE 41 14 733, U.S. Pat. No. 5,334,747).
Diethyl cyclopropane-1,1-dicarboxylate was first prepared by W. H. Perkin (Ber. d. Dt. Chem. Ges., 17 (1884), 54) by means of an intramolecular condensation reaction between diethyl malonate and 1,2-dibromoethane with sodium ethylate as the condensation agent. The yield was 27 to 29% of theory. A. W. Dox and L. Yoder (J.A.C.S., 1921, 2097) were able to increase the yield to 40% of theory, as confirmed by J. M. Stewart and H. H. Westberg (J. Org. Chem., 30 (1965), 1951). One disadvantage of this process is its low yield. The main by-product identified by W. A. Bone and W. H. Perkin (J. Chem. Soc., 67 (1895), 108) is tetraethyl butane-1,1,4,4-tetracarboxylate, which is formed in a competing intermolecular reaction. When using 1,2-dichloroethane, as an alternative to 1,2-dibromoethane, which is a desirable alternative to the 1,2-dibromo compound because it is a cheaper starting material available in industrial quantities, the yield of this by-product can increase to as much as 50% of theory.
Another disadvantage of the process, according to J. M. Stewart and W. H. Westberg, loc. cit., is the difficulty of separating unreacted malonic acid ester by distillation. The authors solved this problem by reacting the malonic acid ester with n-butylamine to give the corresponding n-butyldiamide.
The disadvantages mentioned are considerably alleviated by using potassium carbonate in place of a sodium alcoholate as the condensation agent (D. A. White, Synth. Comm., 7/8 (1977), 559). Yields of dimethyl cyclopropane-1,1-dicarboxylate of 73% of theory are indicated when 1,2-dibromoethane is used. An improved process employs potassium carbonate as the base, with 1,2-dichloroethane as the starting material, and is described in DE 43 26 917. Although the yield ranges up to 85% of theory in this process, carbon dioxide is produced in appreciable amounts, as with all processes using potassium carbonate as condensation agent. This waste gas entrains 1,2-dichloroethane, which is of environmental concern and has to be removed in a special purification step. A need therefore continues to exist for a process for the preparation of cyclopropane-1,1-dicarboxylic acid derivatives from malonic acid derivatives and inexpensive 1,2-dichloro compounds, but produces no waste gas, and which also gives even better yields than the process of DE 43 26 917.